The objective is to determine the mechanisms leading to the anemia of the Belgrade laboratory rat (b), the mottled trait (Mo), hemoglobin deficit (hbd), and sex-linked anemia (sla) in order to identify genetically determined steps in mammalian iron, copper and globin metabolism. The studies of b will include measurement of the incorporation of ferrous and ferric radio-iron into heme by mitochondria, and the examination of the release of 59Fe from transferrin bound to reticulocyte ghosts. The globin synthesis defect of b/b erythroid cells will be explored by the measurement of free heme and the heme controlled repressor, and examination of the effect of hemin on globin synthesis in a cell free system and the efficiency of globin chain initiation and elongation by mRNA. The binding of 125I transferrin to sla/Y isolated intestinal epithelial cells will be measured and the possible synthesis of transferrin by these cells will be examined. A colony of mice with hemoglobin deficit will be established and hematological, iron and globin studies carried out to determine the nature of the primary defect.